Evidence map›Paper›PMID 27165105›Full record

ArticleBreast cancer research : BCR2016

Determining breast cancer histological grade from RNA-sequencing data.

Mei Wang, Daniel Klevebring, Johan Lindberg, Kamila Czene, Henrik Grönberg, Mattias Rantalainen

Open access · goldAbstract read
In one paragraph

Article in Breast cancer research : BCR, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.4field-weighted citation impact, top 20% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 63 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Mei WangDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels Vag 12A, Stockholm, 171 77, Sweden.
Daniel KlevebringDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels Vag 12A, Stockholm, 171 77, Sweden.
Johan LindbergDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels Vag 12A, Stockholm, 171 77, Sweden.
Kamila CzeneDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels Vag 12A, Stockholm, 171 77, Sweden.
Henrik GrönbergDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels Vag 12A, Stockholm, 171 77, Sweden.
Mattias RantalainenDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels Vag 12A, Stockholm, 171 77, Sweden. mattias.rantalainen@ki.se.
Karolinska Institutet · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe histologic grade (HG) of breast cancer is an established prognostic factor. The grade is usually reported on a scale ranging from 1 to 3, where grade 3 tumours are the most aggressive. However, grade 2 is associated with an intermediate risk of recurrence, and carries limited information for clinical decision-making. Patients classified as grade 2 are at risk of both under- and over-treatment.

methodsRNA-sequencing analysis was conducted in a cohort of 275 women diagnosed with invasive breast cancer. Multivariate prediction models were developed to classify tumours into high and low transcriptomic grade (TG) based on gene- and isoform-level expression data from RNA-sequencing. HG2 tumours were reclassified according to the prediction model and a recurrence-free survival analysis was performed by the multivariate Cox proportional hazards regression model to assess to what extent the TG model could be used to stratify patients. The prediction model was validated in N=487 breast cancer cases from the The Cancer Genome Atlas (TCGA) data set. Differentially expressed genes and isoforms associated with HGs were analysed using linear models.

resultsThe classification of grade 1 and grade 3 tumours based on RNA-sequencing data achieved high accuracy (area under the receiver operating characteristic curve = 0.97). The association between recurrence-free survival rate and HGs was confirmed in the study population (hazard ratio of grade 3 versus 1 was 2.62 with 95 % confidence interval = 1.04-6.61). The TG model enabled us to reclassify grade 2 tumours as high TG and low TG gene or isoform grade. The risk of recurrence in the high TG group of grade 2 tumours was higher than in low TG group (hazard ratio = 2.43, 95 % confidence interval = 1.13-5.20). We found 8200 genes and 13,809 isoforms that were differentially expressed between HG1 and HG3 breast cancer tumours.

conclusionsGene- and isoform-level expression data from RNA-sequencing could be utilised to differentiate HG1 and HG3 tumours with high accuracy. We identified a large number of novel genes and isoforms associated with HG. Grade 2 tumours could be reclassified as high and low TG, which has the potential to reduce over- and under-treatment if implemented clinically.

Indexed as

TranscriptomeAdultAgedAged, 80 and overBiomarkers, TumorBreast NeoplasmsComputational BiologyDatabases, Nucleic AcidFemaleGene Expression ProfilingGenetic Association StudiesHumansKaplan-Meier EstimateMiddle AgedNeoplasm GradingNeoplasm MetastasisBiomarkers, TumorBreast neoplasmsIsoformNottingham histologic gradesRNA-seq

Identifiers

PMID27165105
PMCPMC4862203
OpenAlexW2357374211

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.